While a growing body of literature has characterized the physiological and morphological consequences of prenatal ethanol (EtOH) exposure, few studies have examined the influence of such prenatal treatment on subsequent responsiveness to EtOH challenge. Moreover, there is a clear void in the literature pertaining to the influence of prenatal EtOH exposure on subsequent responsiveness to chronic EtOH treatment, particularly as such treatment relates to the development of tolerance and dependence. Given the anomalies in neurochemistry, neuroanatomy, endocrinology, and behavior reported in animals exposed to EtOH prenatally, combined with preliminary data from our laboratory, there is good reason to hypothesize that group differences in EtOH sensitivity should be observed. The general hypothesis being tested is that animals exposed to EtOH in utero will differ from controls in subsequent response to acute and chronic EtOH challenge. To test this hypothesis, a total of ten studies have been designed to investigate the influence of prenatal EtOH exposure on subsequent postnatal sensitivity to (1) acute EtOH challenge, (2) the development and expression of EtOH tolerance, and (3) the development and expression of physical dependence. More specifically, a mouse model system will be used to determine whether prenatal EtOH exposure effects acute sensitivity to EtOH-induced stimulation prenatal EtOH exposure effects acute sensitivity to EtOH- induced stimulation of locomotor activity and EtOH-induced motor incoordination, the development and/or expression of tolerance to the motor incoordinating action of EtOH, and development and/or expression of EtOH dependence, as assessed by intensity of the withdrawal response. Further, additional studies are aimed at identifying potential neurochemical mechanisms underlying altered CNS sensitivity to acute and chronic EtOH challenge by employing a psychopharmacologic approach. Taken together, these studies will fill a critical void in the fetal EtOH literature and begin to address possible CNS mechanisms underlying alteration in neurosensitivity to EtOH in offspring exposed to EtOH in utero.